Variant chr7-100892456-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000665.5(ACHE):c.1431C>T(p.Pro477=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 1,559,426 control chromosomes in the GnomAD database, including 3,938 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1412 hom., cov: 30)

Exomes 𝑓: 0.046 ( 2526 hom. )

Consequence

ACHE
NM_000665.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0170

Variant links:

Genes affected

ACHE (HGNC:108): (acetylcholinesterase (Yt blood group)) Acetylcholinesterase hydrolyzes the neurotransmitter, acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal transmission. It is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen. Acetylcholinesterase exists in multiple molecular forms which possess similar catalytic properties, but differ in their oligomeric assembly and mode of cell attachment to the cell surface. It is encoded by the single ACHE gene, and the structural diversity in the gene products arises from alternative mRNA splicing, and post-translational associations of catalytic and structural subunits. The major form of acetylcholinesterase found in brain, muscle and other tissues is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. The other, alternatively spliced form, expressed primarily in the erythroid tissues, differs at the C-terminal end, and contains a cleavable hydrophobic peptide with a GPI-anchor site. It associates with the membranes through the phosphoinositide (PI) moieties added post-translationally. AChE activity may constitute a sensitive biomarker of RBC ageing in vivo, and thus, may be of aid in understanding the effects of transfusion[provided by RefSeq, Sep 2019]

ACHE links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACHE	NM_000665.5 linkuse as main transcript	c.1431C>T	p.Pro477=	synonymous_variant	3/5	ENST00000241069.11	NP_000656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACHE	ENST00000241069.11 linkuse as main transcript	c.1431C>T	p.Pro477=	synonymous_variant	3/5	1	NM_000665.5	ENSP00000241069	P1	P22303-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15232

AN:

149882

Hom.:

1409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.00776

Gnomad AMR

AF:

0.0661

Gnomad ASJ

AF:

0.0879

Gnomad EAS

AF:

0.000588

Gnomad SAS

AF:

0.0630

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.103

Gnomad NFE

AF:

0.0460

Gnomad OTH

AF:

0.106

GnomAD3 exomes

AF:

0.0580

AC:

13155

AN:

226680

Hom.:

767

AF XY:

0.0568

AC XY:

6920

AN XY:

121898

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.0400

Gnomad ASJ exome

AF:

0.0837

Gnomad EAS exome

AF:

0.000339

Gnomad SAS exome

AF:

0.0595

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.0469

Gnomad OTH exome

AF:

0.0603

GnomAD4 exome

AF:

0.0460

AC:

64903

AN:

1409426

Hom.:

2526

Cov.:

AF XY:

0.0469

AC XY:

32537

AN XY:

693058

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.0456

Gnomad4 ASJ exome

AF:

0.0845

Gnomad4 EAS exome

AF:

0.000284

Gnomad4 SAS exome

AF:

0.0616

Gnomad4 FIN exome

AF:

0.0290

Gnomad4 NFE exome

AF:

0.0394

Gnomad4 OTH exome

AF:

0.0580

GnomAD4 genome

AF:

0.102

AC:

15265

AN:

150000

Hom.:

1412

Cov.:

AF XY:

0.0995

AC XY:

7279

AN XY:

73170

show subpopulations

Gnomad4 AFR

AF:

0.247

Gnomad4 AMR

AF:

0.0657

Gnomad4 ASJ

AF:

0.0879

Gnomad4 EAS

AF:

0.000589

Gnomad4 SAS

AF:

0.0627

Gnomad4 FIN

AF:

0.0288

Gnomad4 NFE

AF:

0.0460

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0598

Hom.:

896

Bravo

AF:

0.110

Asia WGS

AF:

0.0420

AC:

144

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over